The theme of this program project is to develop the scientific bases that are necessary to implement biologically-based risk assessments for several chemicals on the National Priorities List. This will be accomplished by (1) identifying critical mechanisms related to the induction of mutations and cancer by these chemicals, (2) establishing whether or not these mechanisms follow linear or non-linear dose- response relationships between the high doses employed in animal studies and actual or modeled environmental exposures, (4) determining if sensitive populations exist that are not greater or lesser risk to selected chemicals than the general population, (5) developing new methods for determining dermal exposure to hazardous chemicals, (6) investigating factors involved in bioremediation and bioavailability, (7) evaluating mass transfer phenomena in heterogeneous multiphase subsurface systems and enhance methods of remediating such systems, and (8) developing holistochastic human exposure models that integrate space/time distributions of fate and transport with toxicokinetic models linked to human health effects to improve the assessment of risk from hazardous chemicals. The theme addresses many of the stated goals of the Superfund Basic research Program. We will accomplish our task through the investigations proposed in eight research projects and six supporting cores.